The ORF2 glycoprotein of hepatitis E virus inhibits cellular NF-kappaB activity by blocking ubiquitination mediated proteasomal degradation of IkappaBalpha in human hepatoma cells

Background:
Nuclear factor kappa B (NF-kappaB) is a key transcription factor that plays a crucial role in hostsurvival during infection by pathogens. Therefore, it has been a priority of many pathogens tomanipulate the cellular NF-kappaB activity in order to create a favorable environment for theirsurvival inside the host.
Results:
We observed that heterologous expression of the open reading frame 2 (ORF2) protein inhuman hepatoma cells led to stabilization of the cellular I kappa B alpha (IkappaBalpha) pool, with aconcomitant reduction in the nuclear localization of the p65 subunit of NF-kappaB and inhibitionof NF-kappaB activity. Although basal or TPA induced phosphorylation of IkappaBalpha was not altered,its ubiquitination was markedly reduced in ORF2 expressing cells. Further analysis revealedthat ORF2 protein could directly associate with the F-box protein, beta transducin repeatcontaining protein (betaTRCP) and ORF2 over expression resulted in reduced association ofIkappaBalpha...  Read more...

BMC Biochemistry - Latest articles , May 15, 8:00pm